This research is concerned primarily with improving old and developing new techniques applicable to the treatment of human malignancies by modalities including radiotherapy. It involves model studies on three levels: Computer simulation; cultures of density inhibited Chinese hamster cells; and a transplantable mammary sarcoma (EMT-6) in vivo. Specific areas to be investigated include: Repair of potentially lethal lesions after radio-chemotherapy; effects of elevated temperatures, during and after radio-chemotherapy, on cell survival and repair; the investigation, by immunological techniques, of the specific lesions introduced into the DNA by various modalities (particularly by X-irradiation) and their repair; the application of previously developed mathematical techniques to aid in developing new strategies for radio-chemotherapy. To achieve our goals we will utilize standard tissue culture techniques; methods of tumor radiobiology involving in vivo experiments coupled with tissue culture assays; computer simulations of radio-chemotherapy projects. The investigation of specific DNA lesions will utilize the development of anti-sera against specific types of damage and fluorescent techniques to determine antibody binding to the DNA. BIBLIOGRAPHIC REFERENCES: G.M. Hahn, Repair (or recovery) effects in quiescent Chinese hamster cells: an attempt at classification. In Molecular Mechanisms for Repair of DNA, Part B, pp. 601-605 (P.C. Hanawalt and R.B. Setlow, eds.), Plenum Press, N.Y. (1975). H.B. Kal and G.M. Hahn, Kinetic responses of murine sarcoma cells to radiation and hyperthermia in vivo and in vitro. Cancer Res. 36:1923 (1976).